The three-year grant from the Patient-Centered Outcomes Research Institute (PCORI), an independent nonprofit organization based in Washington, D.C., allows the 1-year-old PEDSnet to embark on phase two of a project to create a sustainable pediatric clinical research infrastructure. It aims to integrate data available from eight of the nation’s largest children’s hospital systems with three condition-specific networks and two national data partners.

Most pediatric disorders are rare diseases, so no single pediatric institution usually has enough patients to generate large numbers of study participants. Providing access to diverse, nationally representative health information from millions of children will facilitate a range of study designs and reduce the time and effort needed to launch new studies and accelerate scientific knowledge.

“With our first phase of funding, PEDSnet developed infrastructure for rapid learning with observational studies and clinical trials,” said CHOP’s Christopher Forrest, MD, PhD, who is the principal investigator of PEDSnet and a professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania. “This second phase of funding will enable PEDSnet to reach a high level of operational excellence, ultimately moving into a sustainable research network that advances children’s health through faster and cheaper clinical research.”

Some of the goals for phase two include adding natural language processing expertise for the data coordinating center to use in developing computable phenotypes and outcome measures. The PEDSnet investigators also will strengthen the engagement of parents and clinicians throughout the network to ensure that concerns important to families are research priorities.

Linking data from PEDSnet’s national data partners and regional health plans will allow for the creation of a cohort of patients with complete data available through PEDSnet’s electronic health record data resource.

IBD is a chronic inflammatory disease of the gastrointestinal (GI) tract that can result in ongoing inflammation, leading to a variety of symptoms including diarrhea, abdominal pain and cramping, fatigue, and weight loss. Children with VEO-IBD are a unique population who frequently present with more severe symptoms and greater extent of GI tract involvement than older children and adults with IBD. In addition, these patients tend to respond poorly to conventional IBD therapies used for older patients. These factors suggest that VEO-IBD is a distinct, more aggressive process with a strong genetic contribution to the disease.

“We currently have a cohort of about 250 patients with VEO-IBD, many of whom have significant symptoms that affect their overall quality of life,” said Judith Kelsen, MD, who is a pediatric gastroenterologist and researcher in the Center for Pediatric Inflammatory Bowel Disease at CHOP. “These children were the impetus for the initiation of our research, as we worked to identify therapies to improve their symptoms and treat their disease. We started to realize that VEO-IBD is a different disease with a different etiology, meaning the reasons for having the disease were different than older patients.”

Dr. Kelsen and her colleagues hypothesized that there are strong genetic drivers to the disease involving rare or novel genes. They are using next generation sequencing technology to allow them to detect genetic variants that they believe are enriched in patients with VEO-IBD.

In an article published online in the journal Gastroenterology, the study team reported the results from performing exome sequencing analysis of 125 patients ages 3 weeks to 4 years with VEO-IBD. They identified several novel and rare gene defects in genes associated with primary immunodeficiencies. Some of these pathways are involved in regulation of the immune response, which protects the body from potentially harmful microbes, such as viruses and bacteria.

These gene variants appear to influence both arms of the immune system, the innate response — our body’s first line of defense — and adaptive response — a more sophisticated response that is not immediately activated. The adaptive immune system includes two types of cells, known as B-cells and T-cells. Their jobs are to alert your body to intruders, fight the infection, and then remember the invaders to protect against future attacks. If B- and T-cells are not functioning correctly, they may result in a defective or inappropriate response that contributes to the development of VEO-IBD.

“As we begin to identify the different components of the immune system involved, including B- and T-cell pathways, we can begin to individualize our therapy to the specific patient,” the study authors wrote.

At CHOP, an interdisciplinary team of physicians who specialize in gastroenterology and immunology meet once a month in a VEO-IBD clinic to better target therapies to patients’ underlying genetic defects. Dr. Kelsen and Kathleen Sullivan, MD, PhD, chief of the division of Allergy and Immunology, run the clinic. In many cases, instead of prescribing traditional IBD drugs, they are now using therapies that are directed to diseases of the immune system. Some patients may require more intensive interventions, such as a patient Dr. Kelsen described who is undergoing a stem cell transplant due to the identification of a whole gene deletion (the whole gene is missing) that is critical for the immune system to work appropriately.

Dr. Kelsen also works with Marcella Devoto, PhD, of CHOP’s Division of Human Genetics, and Noor Dawany, PhD, of the department of Biomedical and Health Informatics, to analyze and identify the genes that are responsible for the disease. It is combining the clinical data and the genetics that has proved to be the most successful in treating these children.

As the incidence of VEO-IBD is rising rapidly — accounting for about 6 to 15 percent of pediatric IBD cases — there are many different research avenues to explore, Dr. Kelsen said. In addition to genetic contributors, she and her team, including Maire Conrad, MD, a GI IBD fellow, are studying how differences in the communities of microbes made up of bacteria, viruses, parasites, and fungi that normally reside in our intestinal tract, known as the microbiome, may be partly responsible for triggering the disease. In a study published in August in the journal Inflammatory Bowel Disease, Dr. Kelsen found several bacterial lineages are potentially associated with pediatric Crohn’s disease, a type of IBD.

Families of children with VEO-IBD have been extremely supportive of Dr. Kelsen’s investigations, as she attempts to unravel this complex disease for which there currently is no standard of care for evaluation and treatment.

“I think it is hard at any age to have inflammatory bowel disease, but in many cases, patients with VEO-IBD have a particularly difficult burden due to their young age,” Dr. Kelsen said. “These children often are chronically ill and have not had the opportunity to experience feeling well and participating in everyday childhood activities; therefore, their parents are very willing and generous with their time to help with the research. Without them, we would not be successful in learning more about this disease, so we are incredibly appreciative.”

When people have things in common and cross paths regularly, they often form bonds and become friends. If this were true in the world of biology, then diabetes and mitochondrial disease could become besties.

Mitochondria are organelles that sense and control cells’ energy balance. Certain defects in the way the mitochondria work may lead to diabetes, and the ways our bodies adapt to high blood sugars share many features with the ways our bodies respond to mitochondrial disease.

Exploring these intersections is essential because there are no approved treatments for mitochondrial diseases, which occur in one out of 5,000 people. And any parallels with disorders of energy imbalance, such as diabetes and obesity, could point the way to repurposing drug therapies already on the market for those conditions.

Dr. McCormack made an important observation that children and adolescents with insulin resistance, a factor related to the development of type 2 diabetes, have worse skeletal muscle mitochondria function. A possible explanation is that disrupted mitochondria may not effectively process nutrients and cause decreased insulin action. Without enough insulin, the body cannot move blood sugar (glucose) into the cells. High levels of sugar remain in the bloodstream instead of getting used by muscles.

This leads to a chicken and egg question: “Which problem came first?” Dr. McCormack asked. “Did they develop obesity and insulin resistance, and then their mitochondria got sick? Or are these kids whose mitochondria wasn’t working well to begin with, and that’s why they developed these other problems?”

Dr. McCormack began thinking about her patients who have genetic mutations that cause their mitochondria not to work well. Are individuals who start off with a mitochondrial defect able to balance their blood glucose levels efficiently? With all these intriguing questions and not enough answers in the scientific literature, Dr. McCormack and her study team have launched several research projects.

“In order to test a lot of these hypotheses that sick mitochondria contribute to endocrine disease, and to study the relationship between mitochondrial dysfunction and problems with the way the body handles glucose and predisposes to diabetes, we have to have a good measure of muscle mitochondrial impairment,” Dr. McCormack said. “So our first task was to ask, ‘Does this new technique pick up differences in mitochondrial function in individuals with mitochondrial disease the way we might expect that it does?’ And we’ve had very promising results so far.”

The researchers are expanding the pilot study to include more participants with a wider range of genetic mitochondrial disorders and also to see how children respond to the MRI assessment. Once the study team builds enough evidence to demonstrate that this is a reliable metric of muscle mitochondrial function, it could be used beyond research purposes to potentially improve the diagnostic process and follow how a patient is doing over a course of treatment.

Glycemic Index and Mitochondrial Disease

In a separate study, Dr. McCormack and her study team are looking at how foods’ tendency to raise blood sugar, or glycemic index, relates to mitochondrial disease. Some sources of carbohydrate such as lentils have a low glycemic index and do not raise the blood sugar much when eaten; however, other forms such as soda and juices have a high glycemic index and can elevate the blood sugar quickly. Some people with diabetes pay careful attention to foods’ glycemic index as a nutritional way to manage their disease.

“For patients with mitochondrial disease, for whom we know there is a tendency to develop diabetes more often, there is very little evidence about what those individuals should be eating,” Dr. McCormack said.

She designed a double-blind placebo-controlled crossover study in which participants with mitochondrial disease will arrive on two separate days to consume two different test shakes. The shakes are designed to look and taste similar, and they have an identical amount of carbohydrate, protein, and fat, but they do not have the same glycemic index.

“We would expect that for people with mitochondrial diseases to see a very pronounced rise in blood sugar with a higher glycemic index food because the muscles’ mitochondria don’t work as well,” Dr. McCormack said. “This might suggest that those individuals make food choices guided in part by the food’s glycemic indices.”

Also, a big glycemic excursion that quickly goes up and then comes down may not be optimal for brain metabolism. Dr. McCormack often hears from patients with mitochondrial disease that they feel foggy after consuming high-glycemic meals. So study participants will take attention and working memory tests that allow researchers to measure their cognitive capacity and see if there are any correlates to patients’ reports.

“CHOP is an awesome place to be doing all of this work because of its expertise in each of these areas,” Dr. McCormack said. “And we take care of so many awesome patients and families who volunteer to participate in research and really want to be able to move the care forward.”

Children with JSpA experience inflammation and stiffness of joints that can result in growth disturbances and loss of range of motion if not controlled properly. They tend to develop arthritis of lower extremities and are as at risk of developing arthritis of the lower back or spine. JSpA is associated with more frequent and higher intensity pain and poorer quality of life than other categories of juvenile arthritis.

“One of the questions we always get is, ‘Do a lot of kids actually have arthritis?’” said Dr. Weiss, clinical research director for CHOP’s division of rheumatology. “Actually, our clinic is full of these children. Our treatments are so effective that unless our patients chose to share that they have a chronic condition, most of the time no one knows there’s anything wrong with them.”

Juvenile arthritis is the most common rheumatologic disease among children, ranging from one to four cases per 1,000 children, which is about the same prevalence as Type 1 diabetes mellitus and cystic fibrosis in children. JSpA accounts for about 20 percent of childhood arthritis.

Dr. Weiss’ research concentrates on characterizing the disease features of children with JSpA, with a focus on enthesitis (inflammation of the tendon insertions) and arthritis of the lower back. She has an ongoing project evaluating the uses and effects of drugs for this condition. Recently she led an international effort to develop and validate a disease activity score for children with JSpA based on input from more than 100 physicians.

“This disease activity score is a really important metric because we need to gauge whether our patients are getting better on treatment or not,” Dr. Weiss said. “Prior to the development of this score, no metrics existed for these kids.”

Dr. Weiss also conducted a study that determined using ultrasound is more reliable than physical exams for accurate diagnosis of enthesitis. This is crucial because detection of enthesitis influences disease classification and subsequent treatment decisions.

In July, Dr. Weiss published results from another study that focused on determining how many children with newly diagnosed JSpA develop early lower back arthritis. Her team found that 20 percent of children had imaging evidence of lower back arthritis within six months of diagnosis, and that the majority of these children did not have the traditional symptoms used to screen for this condition, including back pain.

“Looking at kids at diagnosis to see if they have early arthritis of the lower back could impact the rapidity with which we start medications and could potentially alter their entire disease course,” Dr. Weiss said.

Currently, Dr. Weiss is analyzing data from a large database she created that includes children with enthesitis-related arthritis from five pediatric rheumatology practices, including one in Italy. She is exploring the effectiveness of treatment strategies for newly diagnosed patients.

When she is not improving children’s outcomes through research, Dr. Weiss has leadership roles within several national organizations dedicated to finding treatments and improving care for pediatric rheumatic diseases. One of her major projects was leading an update of the American College of Rheumatology’s juvenile arthritis treatment guidelines published in 2013. She is a member of the literature review team for the American College of Rheumatology’s spondyloarthritis treatment guidelines that will be published later in 2015.

Dr. Weiss also is the principal investigator at CHOP for a new national registry launching this summer by the Childhood Arthritis & Rheumatology Research Alliance (CARRA). About 60 sites are participating, and the data collection will be geared toward monitoring the long-term safety of medications prescribed for pediatric patients.

“I want to make kids better, but with the least amount of side effects,” said Dr. Weiss, who is co-chair of the Juvenile Idiopathic Arthritis Research Committee for CARRA. “In rheumatology, there are so many new drugs coming on the market, yet pediatrics is always behind adult medicine in terms of approval for the drugs. So there is a lot of work to be done to make sure the new medications are both effective and safe for our kids.”

Dr. Weiss shares her passion for rheumatology by acting as a mentor for fellows who are interested in pursuing research in this area, and she presents lectures to CHOP residents on pediatric rheumatology topics.

“By doing a combination of research and clinical care, I feel like I’m doing something different and meaningful every single day, and I love all aspects of it,” Dr. Weiss said.

Urinary tract infections (UTI) are common bacterial infections that are not only aggravating for youngsters and their parents, but they also can have serious long-term consequences. That is why it is valuable for clinicians to be able to better predict which children are most susceptible to repeated UTIs.

Instigated by a buildup of bacteria in the urine, UTIs cause uncomfortable burning with urination, abdominal pain, and frequent urination or wetting accidents. If the bacterial infection reaches the kidneys, symptoms also may include a fever, lack of appetite, and irritability. Most UTIs do not lead to complications with proper treatment, but permanent scarring of the kidneys may occur in severe cases. The Children’s Hospital of Philadelphia treats more than 800 patients with UTIs each year.

“We think that about 5 percent of kids in the first five, six years of life are going to have a urinary tract infection,” Dr. Keren said. “The focus of clinicians and researchers for the last few decades regarding children who have had UTIs has been on VUR, but there has been very little attention paid to children who don’t have VUR.”

VUR is a condition during urination when the bladder contracts and some of the urine flows up the ureters back toward the kidneys where the urine came from. VUR allows bacteria that may be in the bladder to travel with the refluxing urine to the kidney.

Bladder dysfunction often occurs when a child gets into a habit of holding in urine for long periods, which stretches the bladder so much that it does not empty completely. Bacteria have the chance to multiply in residual urine left over in the bladder after incomplete voiding.

In a previous study, called the Randomized Intervention for Vesicoureteral Reflux (RIVUR) study, children with VUR who had a UTI were randomized to receive daily prophylaxis with antibiotic or placebo. Dr. Keren and his colleagues also conducted a complementary study, called the Careful Urinary Tract Infection Evaluation (CUTIE), in which they compared 305 children from the RIVUR placebo group to another cohort of 195 children who had UTIs but did not have VUR. They observed the children in the two CUTIE groups for two years.

“For the first time, we could follow the natural history of what happens to kids who have had a first or second UTI and aren’t getting any therapy,” Dr. Keren said. “And we could see how much of a differentiator VUR is in terms of subsequent UTIs.”

The rate of recurrent UTIs in children who did have VUR was 25 percent; however, the highest risk of recurrent UTIs was for children who had a combination of any degree of VUR and BBD: 56 percent. If the child only had BBD, the rate was still high: 35 percent. The association between BBD and an increased risk of recurrent UTIs is noteworthy because BBD was a common problem among children enrolled in CUTIE: 59 percent (with VUR) and 46 percent (no VUR).

These observations support the researchers’ suspicions that BBD can be a key driver of UTIs. If future larger studies validate CUTIE’s findings, it may give clinicians evidence in order to tailor their treatment approaches and help families decide whether the benefits of daily prophylaxis outweigh the risks and inconvenience.

“The idea is to move toward a more individualized but data-driven approach to decide who should and shouldn’t get prophylaxis,” Dr. Keren said.

For example, urologists who run the DOVE Center for Voiding and Bladder Function at The Children’s Hospital of Philadelphia give prophylactic antibiotics to children who are undergoing bowel and bladder retraining to prevent UTI recurrences. The program uses behavior modification techniques to teach children to regain bowel and bladder control, and UTIs likely would sidetrack their success.

About 79 million Americans are currently infected with human papillomavirus (HPV), and 14 million people become newly infected each year. Yet, despite these very real numbers, misconceptions about HPV seem to overshadow attempts to increase vaccination rates to prevent infection. In 2014, coverage estimates for HPV continued to lag behind other routine immunizations recommended for adolescents’ ages 11 and 12, according to the Centers for Disease Control’s Morbidity and Mortality Weekly Report.

Three vaccines that protect against HPV infection are currently available in the U.S. The quadrivalent (HPV4) and bivalent (HPV2) vaccines protect against HPV types 16 and 18, which cause 70 percent of cervical cancers; HPV4 also protects against HPV types 6 and 11, which cause 90 percent of genital warts. The newly introduced nonavalent vaccine (HPV9) includes an additional five serotypes that increases overall coverage to more than 85 percent of cervical cancers.

HPV is a sexually transmitted infection that can be spread by having oral, vaginal, or anal sex with someone who has the virus. It is so common that nearly all sexually active men and women get or are exposed to it at some point in their lives.

These are some of the important facts that will be conveyed in an educational video being tested at The Children’s Hospital of Philadelphia. It is geared toward 11 to 17 year olds and aims to improve parents’ and teens’ acceptance of HPV vaccination. Kristen Feemster MD, MPH, MSHP, principal investigator for the study, helped to develop the content in collaboration with a medical education company that is producing the video.

“I think a video-based education tool could be helpful,” said Dr. Feemster, a faculty member at PolicyLab at CHOP and an assistant professor of Pediatrics in the division of Infectious Diseases at the Perelman School of Medicine at the University of Pennsylvania. “It’s interactive, and it’s coming from a different voice. The video includes images of teens, and cartoon images to illustrate the HPV virus. I think all of those methods help get the message across.”

The study will include about 300 participants who will be randomized to either receive routine care, which is receipt of the HPV Vaccine Information Statement (VIS), or to receive the VIS in addition to viewing the educational video. The study team expects to begin data analysis by the end of this year.

“We are hoping to see an impact,” Dr. Feemster said. “The video is shown before the provider comes in to make a recommendation, so this is not the only thing that will drive their decision making.”

If the study shows that the education video is effective, it eventually could be disseminated to clinicians as a helpful cancer prevention resource to addresses parents’ and teens’ questions regarding HPV vaccine safety and efficacy in a format that teens are comfortable using.

For example, boys may think that they do not need to be vaccinated against HPV because they cannot develop cervical cancer. Actually, the vaccine protects against HPV strains that also can help prevent penile, anal, and oropharyngeal cancers. Also, since sexual partners can be exposed to the disease, vaccinating males and females helps to increase the protection of others against cancers associated with HPV.

“You receive great individual protection from the vaccine, but to block transmission it helps to have as many people vaccinated as possible,” Dr. Feemster said. “This vaccine has a potential to make a significant public health impact globally and understanding ways to implement recommendations will be really important.”

According to the Center for Disease Control and Prevention, about 360,000 people in the U.S. get genital warts each year and more than 11,000 women in the U.S. get cervical cancer each year. These numbers seem unnecessarily high when a safe and effective vaccination to prevent HPV transmission has been available since 2006.

A compilation of common questions and answers about HPV and the vaccine is available on The Children’s Hospital of Philadelphia’s website.

More than 1,500 children die from abuse in the U.S each year, and many more are injured. Hospitals, however, may be missing opportunities to protect these young victims of abuse.

A study published in the August issue Pediatrics showed a wide variation in how hospitals screen for hidden injuries, also called “occult injuries,” in young children with a diagnosis of physical abuse. These are injuries, such as cracked ribs or brain injuries, which may not be seen immediately during a physical exam and are only discovered via screening imaging. A series of X-rays, called a skeletal survey, are recommended by American Academy of Pediatrics guidelines for children younger than 2 years with fractures suspicious for child abuse.

The study results revealed that out of 2,500 children under 2 years old with an abuse diagnosis, only half (48 percent) were evaluated for occult fractures using skeletal surveys. The data showed a wide variation in evaluation practices among the 366 U.S. hospitals included in the study. None of the infants underwent a skeletal survey at some hospitals, while all of the infants underwent a skeletal survey at other hospitals.

A 2012 study also led by Dr. Wood revealed variation in rates of skeletal surveys performed at 40 large pediatric hospitals — 55 percent to 93 percent — but overall, 83 percent of the children received a skeletal survey. In the current study, the investigators looked at primarily non-pediatric focused hospitals. They noted that the majority of injured children receive care at these general hospitals, which are less likely to have specialized child abuse consultants than pediatric centers.

Taking into account previous research estimates of the percentage of children expected to have occult fractures revealed on skeletal surveys, Dr. Wood and her co-authors suggest that one of every seven or eight children who participated in the study sample may have had undiagnosed occult fractures.

At CHOP, Dr. Wood is a faculty member of PolicyLab, an attending physician in the division of general pediatrics, and director of research for Safe Place: Center for Child Protection and Health. She also is an assistant professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania. The study team included Benjamin French, PhD, of biostatistics and epidemiology at Upenn; Lihai Song of healthcare analytics for PolicyLab; and Chris Feudtner, MD, MPH, PhD, an attending physician in CHOP’s division of general pediatrics and director of CHOP’s department of medical ethics.

It is imperative for clinicians to detect and treat seizures that may occur in newborns with congenital heart disease (CHD) who have cardiac surgery. Seizures are associated with underlying brain injury, greater illness severity, and worse neurodevelopmental outcomes. The problem is that seizures can be difficult to identify during a routine bedside clinical assessment.

Continuous postoperative encephalographic (EEG) monitoring can show physicians when these medically fragile patients are experiencing a seizure by measuring the electrical activity in their brains. Yet, many centers do not follow professional guidelines issued in 2011 by The American Clinical Neurophysiology Society (ACNS) that call for continuous EEG monitoring of neonates undergoing surgery for CHD.

“We found that continuous EEG monitoring identified newborns who had seizures, which indicated underlying brain injury, and are a risk factor for worse neurodevelopmental outcomes and mortality,” said study leader Maryam Y. Naim, MD, an attending physician in CHOP’s Pediatric Cardiac Intensive Care Unit. The majority of the seizures found using EEG would not have been visible to clinical caregivers, she added.

Over an 18-month period, the researchers studied 161 newborns with CHD who underwent open heart surgery at CHOP and received continuous EEG monitoring as part of routine postoperative monitoring. The study team found seizures in 13 of the infants (8 percent). Of those 13 infants, 11 (85 percent) had subclinical seizures, detectable only by EEG. Eight of the 13 infants had status epilepticus seizures, which are particularly dangerous. Five of the 13 infants with seizures died, which is a mortality rate of 38 percent, compared to four deaths among the 148 infants who did not have seizures (3 percent).

“Recognizing these seizures early is crucial for implementing treatments to prevent their recurrence,” Dr. Naim said, although she acknowledged that investigators have not yet demonstrated that treating seizures will improve long-term outcomes in high-risk pediatric heart patients.

An editorial commentary that accompanied the study calls for a larger, multicenter study to analyze continuous EEG monitoring following infant heart surgery and to investigate seizure prevention and treatment. The commenters also advocate for a less expensive and less labor-intensive screening tool than continuous EEG monitoring.

Many autoimmune diseases run in families, and because individual patients often have more than one autoimmune condition, clinicians have long suspected that these disorders have shared genetic predispositions. An international study team led by researchers from The Children’s Hospital of Philadelphia’sCenter for Applied Genomics focused on 10 autoimmune diseases that begin in childhood and found that they indeed have genetic overlaps.

The investigators found 27 genome-wide loci, including five novel loci, among the diseases examined. Of those 27 signals, 22 were shared by at least two of the autoimmune diseases, and 19 of them were shared by at least three of them. The results appeared online in Nature Medicine.

“Our approach did more than finding genetic associations among a group of diseases,” said study leader, Hakon Hakonarson, MD, PhD, director of the Center for Applied Genomics at CHOP. “We identified genes with a biological relevance to these diseases, acting along gene networks and pathways that may offer very useful targets for therapy.”

The meta-analysis included a case-control study of 6,035 subjects with automimmune disease and 10,700 controls, all of European ancestry. The study’s lead analyst, Yun (Rose) Li, an MD/PhD graduate student at the University of Pennsylvania and the Center for Applied Genomics mentored by Dr. Hakonarson and his research team, applied highly innovative and integrative approaches in supporting the study of pathogenic roles of the genes uncovered across multiple diseases.

“Rather than looking at overall gene expression in all cells, we focused on how these genes upregulated gene expression in specific cell types and tissues, and found patterns that were directly relevant to specific diseases,” said Dr. Hakonarson, who also is on the faculty of the Perelman School of Medicine at the University of Pennsylvania. “For instance, among several of the diseases, we saw genes with stronger expression in B cells. Looking at diseases such as lupus or juvenile idiopathic arthritis, which feature dysfunctions in B cells, we can start to design therapies to dial down over-expression in those cells.”

Many of the gene signals the investigators discovered were on biological pathways functionally linked to cell activation, cell proliferation, and signaling systems important in immune processes. Identifying specific autoimmune diseases’ genetic architecture gives researchers opportunities to better target potential therapies, including the possibility of repurposing existing drugs available for non-autoimmune diseases.

Funds from the National Institutes of Health, the Wellcome Trust, the Paul and Daisy Soros Fellowship for New Americans, the Crohn’s & Colitis Foundation of America, the Juvenile Diabetes Research Foundation, the Lupus Research Institute, and Institutional Development Funds from The Children’s Hospital of Philadelphia supported this research.